Adult respiratory distress syndrome (ARDS) is a grave complication in critically ill patients resulting in severe pulmonary dysfunction and death. This research proposal aims to elucidate novel pathophysiologic mechanism(s) of ARDS using a combination of in vivo, ex vivo, in vitro and clinical investigations. In a previous study, adaptation of Differential Display Reverse Transcriptase Polymerase Chain Reaction (DDRT-PCR) to total RNA derived from rat ARDS (IL-2-induced) lungs has led to the identification of a highly inducible and novel gene termed mob-1, a member of the rat a-chemokine family. The broad, long term objective of this proposal is to confirm a central role for mob-1 in the development of ARDS and to test the hypothesis that mob-1 acts by promoting leukocyte recruitment to the injured lung and by modulating angiogenesis, a vital phase in the resolution of ARDS. Five specific aims are proposed as a basis for this research: First, to characterize and localize pulmonary mob-1 expression using a highly-reproducible animal model of ARDS-like microvascular lung injury induced by IL-2 infusion. Second, to determine if the purported human homologue of mob-1, termed IP-10, can be detected in BAL fluid derived from ARDS patients. Third, to express recombinant mob-1 as a biologically active, secreted protein in E. coli cells for use in functional studies as well as an immunogen to generate anti-mob-1 antibodies. Fourth, to investigate if administration of recombinant mob-1 exhibits chemotactic properties using an in vitro fluorescent transwell migration assay and examine whether mob-1 affects angiogenesis utilizing a rat aortic ring model. Confirmation that pulmonary mob-1 exerts a central role in the pathogenesis of experimental ARDS could lead to the development of novel organ-specific pharmacological strategies to combat clinical ARDS such as the intra-tracheal administration of mob-1 inhibitors.